ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΠ»ΠΈ Src-ΠΊΠΈΠ½Π°Π·Ρ ΠΈ ΡΠΎΡΡΠ°ΡΠΈΠ΄ΠΈΠ»ΠΈΠ½ΠΎΠ·ΠΈΡΠΎΠ»-3-ΠΊΠΈΠ½Π°Π·Ρ Π² ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² ΡΠΏΠΈΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ°
ΠΠ°Π²ΠΈΡΠΈΠΌΠΎΡΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΈ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π΅Π³ΠΎ Π’Π ΡΠΊΠ°Π·ΡΠ²Π°Π΅Ρ Π½Π° ΡΠΎ, ΡΡΠΎ Π±Π΅Π»ΠΊΠΈ-ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΡ ΡΡΠΈΡ ΡΡΠ°Π΄ΠΈΠΉ ΡΠ²Π»ΡΡΡΡΡ Π΅Π΅ ΡΡΠ±ΡΡΡΠ°ΡΠ°ΠΌΠΈ. Π‘Π΅ΠΉΡΠ°Ρ ΠΈΠ·Π²Π΅ΡΡΠ΅Π½ ΡΠ΅Π»ΡΠΉ ΡΡΠ΄ ΡΠ°ΠΊΠΈΡ ΡΡΠ±ΡΡΡΠ°ΡΠΎΠ². ΠΡΠΎ Π°Π΄Π°ΠΏΡΠΎΡΠ½ΡΠ΅ Π±Π΅Π»ΠΊΠΈ She, GRB2, ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΡΠ΅ ΡΠ°ΠΊΡΠΎΡΡ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° STAT, ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠ°Π·Π° Π‘Ρ (Π€ΠΠ‘Ρ), ΡΠΎΡΡΠ°ΡΠΈΠ΄ΠΈΠ»ΠΈΠ½ΠΎΠ·ΠΈΡΠΎΠ»-3-ΠΊΠΈΠ½Π°Π·Π° (Π€Π-Π-Π) ΠΈ Src-ΠΊΠΈΠ½Π°Π·Π°, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΡΠ΄ Π΄ΡΡΠ³ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² (Moghal, Sternberg… Π§ΠΈΡΠ°ΡΡ Π΅ΡΡ >
- Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- ΠΡΠ΄Π΅ΡΠΆΠΊΠ°
- ΠΠΈΡΠ΅ΡΠ°ΡΡΡΠ°
- ΠΡΡΠ³ΠΈΠ΅ ΡΠ°Π±ΠΎΡΡ
- ΠΠΎΠΌΠΎΡΡ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈ
Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- Π‘ΠΠΠ‘ΠΠ Π‘ΠΠΠ ΠΠ©ΠΠΠΠ
- 1. ΠΠΠΠΠΠΠΠ
- 2. ΠΠΠΠΠ ΠΠΠ’ΠΠ ΠΠ’Π£Π Π«
- 2. 1. ΠΠΏΠΈΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΡΠΉ ΡΠ°ΠΊΡΠΎΡ ΡΠΎΡΡΠ° ΠΈ Π΅Π³ΠΎ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ
- 2. 2. Π Π΅ΡΠ΅ΠΏΡΠΎΡ-ΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΡΠΉ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·
- 2. 2. 1. ΠΠ΅Π»ΠΊΠΈ, ΡΠ΅Π³ΡΠ»ΠΈΡΡΡΠΈΠ΅ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·
- 2. 2. 2. ΠΠ½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ ΠΊΠΎΠΌΠΏΠ°ΡΡΠΌΠ΅Π½ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΡ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ²
- 2. 2. 3. Π’Π΅ΠΎΡΠΈΠΈ Π±ΠΈΠΎΠ³Π΅Π½Π΅Π·Π° ΡΠ½Π΄ΠΎΡΠΎΠΌ
- 2. 3. Π Π΅ΡΠ΅ΠΏΡΠΎΡΡ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° ΠΠ³Π¬Π ΠΈ ΠΈΡ Π»ΠΈΠ³Π°Π½Π΄Ρ
- 2. 4. Π‘ΠΈΠ³Π½Π°Π»ΡΠ½ΡΠ΅ ΠΏΡΡΠΈ, ΡΡΠΈΠΌΡΠ»ΠΈΡΡΠ΅ΠΌΡΠ΅ ΠΠ€Π
- 2. 5. ΠΠ·Π°ΠΈΠΌΠΎΡΠ²ΡΠ·Ρ ΠΌΠ΅ΠΆΠ΄Ρ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·ΠΎΠΌ ΠΈ ΠΏΠ΅ΡΠ΅Π΄Π°ΡΠ΅ΠΉ ΡΠΈΠ³Π½Π°Π»Π°
- 2. 6. ΠΠΈΠ½Π°Π·Ρ Π²Π³Ρ-ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π°
- 2. 6. 1. Π‘ΡΡΡΠΊΡΡΡΠ½ΡΠ΅ Π΄ΠΎΠΌΠ΅Π½Ρ ΠΊΠΈΠ½Π°Π· Π²Π³Ρ-ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π°
- 2. 6. 2. ΠΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΊΠΈΠ½Π°Π· ΠΠ³Ρ-ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π°
- 2. 7. Π€ΠΎΡΡΠ°ΡΠΈΠ΄ΠΈΠ»ΠΈΠ½ΠΎΠ·ΠΈΡΠΎΠ»-Π-ΠΊΠΈΠ½Π°Π·Ρ
- 2. 7. 1. ΠΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ Π€Π-Π-ΠΊΠΈΠ½Π°Π·
- 2. 7. 2. Π ΠΎΠ»Ρ Π€Π-Π-Π Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΏΠΎΡΡΠ΅Π΄ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π°
- 2. 7. 2. 1. Π ΠΎΠ»Ρ Π€Π-Π-ΠΊΠΈΠ½Π°Π· Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΡΠ½ΠΊΡΠΈΠΉ ΡΠ°Π½Π½ΠΈΡ ΡΠ½Π΄ΠΎΡΠΎΠΌ
- 2. 7. 2. 2. Π ΠΎΠ»Ρ Π€Π-Π-ΠΊΠΈΠ½Π°Π· Π² ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΠΈ ΠΌΡΠ»ΡΡΠΈΠ²Π΅Π·ΠΈΠΊΡΠ»ΡΡΠ½ΡΡ ΡΠ΅Π»
- 3. 1. ΠΠ»Π΅ΡΠΎΡΠ½ΡΠ΅ Π»ΠΈΠ½ΠΈΠΈ
- 3. 2. ΠΠ±ΡΠ°Π±ΠΎΡΠΊΠ° ΠΊΠ»Π΅ΡΠΎΠΊ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ°ΠΌΠΈ
- 3. 3. ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΉΠΎΠ΄ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΠΠ€Π
- 3. 4. ΠΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΡ ΠΏΠΎ ΡΡΠΈΠΌΡΠ»ΡΡΠΈΠΈ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π°
- 3. 5. ΠΠ½Π°Π»ΠΈΠ· ΡΠ΅ΡΠΈΠΊΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ
- 3. 6. Π‘ΡΠ±ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ΅ ΡΡΠ°ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π² Π³ΡΠ°Π΄ΠΈΠ΅Π½ΡΠ΅ ΠΏΠ»ΠΎΡΠ½ΠΎΡΡΠΈ ΠΠ΅ΡΠΊΠΎΠ»Π»Π°
- 3. 7. ΠΠΎΠ½ΡΡΠ°Π½ΡΡ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π°
- 3. 8. ΠΠΌΠΌΡΠ½ΠΎΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΠΎΠ΅ ΠΎΠΊΡΠ°ΡΠΈΠ²Π°Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ
- 3. 9. ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π½ΠΎΠΉ ΠΈ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΡΠ°ΠΊΡΠΈΠΉ
- 3. 10. ΠΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠ°Π·Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ²
- 3. 11. ΠΠΌΠΌΡΠ½ΠΎΠ±Π»ΠΎΡΡΠΈΠ½Π³
- 3. 12. ΠΠ½ΡΠΈΡΠ΅Π»Π°
- 4. 1. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΠ»ΠΈ Src-ΠΊΠΈΠ½Π°Π·Ρ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π° ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ
ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ²
- 4. 1. 1. ΠΠ½Π°Π»ΠΈΠ· Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠΈ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Ρ Π½ΠΎΠΊΠ°ΡΡΠΎΠΌ Π³Π΅Π½Π° Src
- 4. 1. 2. ΠΠ½Π°Π»ΠΈΠ· ΡΡΠ°ΡΡΠΈΡ Src-ΠΊΠΈΠ½Π°Π·Ρ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π΄Π΅Π³ΡΠ°Π΄Π°ΡΠΈΠΈ 1251-ΠΠ€Π
- 4. 1. 3. ΠΠ½Π°Π»ΠΈΠ· Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΠΈ ΡΠ΅ΡΠΈΠΊΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ WT ΠΈ PURO
- 4. 1. 4. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° ΠΊΠΈΠ½Π°Π· Src-ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° CGP77675 Π½Π° ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ· ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ HER14 ΠΈ ΠΠ‘
- 4. 1. 5. ΠΠΌΠΌΡΠ½ΠΎΡΠ»ΡΠΎΡΠ΅ΡΡΠ΅Π½ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² ΠΏΡΠΈ Π΄Π΅ΠΉΡΡΠ²ΠΈΠΈ CGP
- 4. 1. 6. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ°ΡΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΠΊΠ»Π°ΡΡΠΈΠ½Π° ΠΏΠΎΡΠ»Π΅ ΡΡΠΈΠΌΡΠ»ΡΡΠΈΠΈ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π° ΠΠ€Π Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π431, WT ΠΈ PURO
- 4. 2. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΠ»ΠΈ ΡΠΎΡΡΠ°ΡΠΈΠ΄ΠΈΠ»ΠΈΠ½ΠΎΠ·ΠΈΡΠΎΠ»-3-ΠΊΠΈΠ½Π°Π·Ρ Π² ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π΅ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ
ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ²
- 4. 2. 1. ΠΠ½Π°Π»ΠΈΠ· Π²Π»ΠΈΡΠ½ΠΈΡ Π²ΠΎΡΡΠΌΠ°Π½Π½ΠΈΠ½Π° Π½Π° Π΄ΠΈΠ½Π°ΠΌΠΈΠΊΡ ΠΊΠΎΠΌΠΏΠ°ΡΡΠΌΠ΅Π½ΡΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΠ€Π Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π
- 4. 2. 2. Π‘ΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΡΡΡΠ΅ΠΊΡΠ° Π²ΠΎΡΡΠΌΠ°Π½Π½ΠΈΠ½Π° ΠΏΡΠΈ Π½ΠΈΠ·ΠΊΠΈΡ (1 Π½Π³/ΠΌΠ») ΠΈ Π²ΡΡΠΎΠΊΠΈΡ (200 Π½Π³/ΠΌΠ») ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ ΠΠ€Π
- 4. 2. 3. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π° ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² ΠΏΡΠΈ Π΄Π΅ΠΉΡΡΠ²ΠΈΠΈ Π²ΠΎΡΡΠΌΠ°Π½Π½ΠΈΠ½Π° Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΌΠ΅ΡΠΎΠ΄Π°
ΠΠΠ — ΡΠ½Π΄ΠΎΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠ΅ΡΠΈΠΊΡΠ»ΡΠΌ (ER, endoplasmic reticulum) — ΠΠ€Π — ΡΠΏΠΈΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΡΠΉ ΡΠ°ΠΊΡΠΎΡ ΡΠΎΡΡΠ° (EGF, epidermal growth factor) — ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ — ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ ΡΠΏΠΈΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° (EGF-R, receptor of epidermal growth factor) —
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΠ»ΠΈ Src-ΠΊΠΈΠ½Π°Π·Ρ ΠΈ ΡΠΎΡΡΠ°ΡΠΈΠ΄ΠΈΠ»ΠΈΠ½ΠΎΠ·ΠΈΡΠΎΠ»-3-ΠΊΠΈΠ½Π°Π·Ρ Π² ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² ΡΠΏΠΈΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ° (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
ΠΠΏΠΈΠ΄Π΅ΡΠΌΠ°Π»ΡΠ½ΡΠΉ ΡΠ°ΠΊΡΠΎΡ ΡΠΎΡΡΠ° (ΠΠ€Π ) ΠΎΡΠ½ΠΎΡΠΈΡΡΡ ΠΊ Π³ΡΡΠΏΠΏΠ΅ ΠΏΠΎΠ»ΠΈΠΏΠ΅ΠΏΡΠΈΠ΄Π½ΡΡ ΡΠΎΡΡΠΎΠ²ΡΡ ΡΠ°ΠΊΡΠΎΡΠΎΠ², ΡΠ΅Π³ΡΠ»ΠΈΡΡΡΡΠΈΡ ΠΏΡΠΎΠ»ΠΈΡΠ΅ΡΠ°ΡΠΈΡ, Π΄ΠΈΡΡΠ΅ΡΠ΅Π½ΡΠΈΡΠΎΠ²ΠΊΡ ΠΈ Π°ΠΏΠΎΠΏΡΠΎΠ· ΡΠ°Π·Π½ΡΡ ΡΠΈΠΏΠΎΠ² ΠΊΠ»Π΅ΡΠΎΠΊ. ΠΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΠ€Π Π½Π° ΠΊΠ»Π΅ΡΠΊΠΈ ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠ΅ΡΠ΅Π· ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΠΉ ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΊΠΈΠ½Π°Π·Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ ΠΈ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΈΠΌΠΈ ΡΠ°ΠΉΡΠ°ΠΌΠΈ Π°Π²ΡΠΎΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ, Π½Π°Ρ ΠΎΠ΄ΡΡΠΈΠΌΠΈΡΡ Π½Π° Π‘-ΠΊΠΎΠ½ΡΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°. ΠΡΠΈ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠΈ ΠΠ€Π ΡΠΎ ΡΠ²ΠΎΠΈΠΌ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΌ Π½Π° ΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Π΅ (ΠΠ) ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ Π΄Π²Π° ΡΡΠ΄Π° ΡΠΎΠ±ΡΡΠΈΠΉ. ΠΠΎ-ΠΏΠ΅ΡΠ²ΡΡ , ΠΈΠ½ΠΈΡΠΈΠΈΡΡΡΡΡΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΠ΅ ΠΊΠ°ΡΠΊΠ°Π΄Ρ, Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠ΅Π³ΠΎ ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π½ΡΡ Π³Π΅Π½ΠΎΠ² (Fantl et al., 1993). Π ΡΡΠΎΠΌ ΠΏΡΠΎΡΠ΅ΡΡΠ΅ ΠΊΠ»ΡΡΠ΅Π²ΡΡ ΡΠΎΠ»Ρ ΠΈΠ³ΡΠ°Π΅Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΠΈΡΠΎΠ·ΠΈΠ½ΠΊΠΈΠ½Π°Π·Ρ (Π’Π) ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°: ΠΎΠ½Π° ΡΡΠΈΠΌΡΠ»ΠΈΡΡΠ΅Ρ ΡΠ΅Π»ΡΠΉ ΡΡΠ΄ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ Π±Π΅Π»ΠΊΠΎΠ², ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΡΡ ΠΈΡ ΠΏΠΎ ΡΠΈΡΠΎΠ·ΠΈΠ½Ρ. ΠΠΎ-Π²ΡΠΎΡΡΡ , Π»ΠΈΠ³Π°Π½Π΄-ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΠ΅ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΡ ΠΏΠΎΠ΄Π²Π΅ΡΠ³Π°ΡΡΡΡ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Ρ (Beguinot et al., 1984; ΠΠΈΠΊΠΎΠ»ΡΡΠΊΠΈΠΉ ΠΈ Π΄Ρ., 1987; Ullrich, Schiessenger, 1990). Π Π½Π°ΡΡΠΎΡΡΠ΅ΠΌΡ Π²ΡΠ΅ΠΌΠ΅Π½ΠΈ ΠΌΠΎΠΆΠ½ΠΎ ΡΡΠΈΡΠ°ΡΡ ΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½Π½ΡΠΌ, ΡΡΠΎ Π’Π ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΠ° Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ Π΄Π»Ρ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΡ ΡΠΈΠ³Π½Π°Π»Π°, ΠΎΠ½Π° ΡΠ°ΠΊΠΆΠ΅ ΡΡΠ°ΡΡΠ²ΡΠ΅Ρ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΈ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΈ Π΅Π³ΠΎ Π½Π° ΠΏΡΡΡ Π΄Π΅Π³ΡΠ°Π΄Π°ΡΠΈΠΈ (ΠΠ»Π°Π³ΠΎΠ²Π΅ΡΠ΅Π½ΡΠΊΠ°Ρ ΠΈ Π΄Ρ., 1994; Π‘ΠΎΠΊΠΎΠ»ΠΎΠ²Π° ΠΈ Π΄Ρ., 1995; Kornilova et al., 1996).
ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΠ΅ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΡ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·ΡΡΡΡΡ Π² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΌ ΡΠ΅ΡΠ΅Π· ΠΊΠ»Π°ΡΡΠΈΠ½-ΠΎΠΊΠ°ΠΉΠΌΠ»Π΅Π½Π½ΡΠ΅ ΡΠΌΠΊΠΈ (ΠΠ―) ΠΈ ΠΏΠΎΠΏΠ°Π΄Π°ΡΡ Π² ΡΠ°Π½Π½ΠΈΠ΅ ΡΠ½Π΄ΠΎΡΠΎΠΌΡ, Π³Π΄Π΅ ΠΈ ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ ΠΈΡ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠ°: ΡΠ°ΡΡΡ Π»ΠΈΠ³Π°Π½Π΄-ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² ΠΏΠΎΠΏΠ°Π΄Π°Π΅Ρ Π² ΠΏΠΎΠ·Π΄Π½ΠΈΠ΅ ΡΠ½Π΄ΠΎΡΠΎΠΌΡ, ΠΈ Π² Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅ΠΌ ΠΏΠΎΠ΄Π²Π΅ΡΠ³Π°Π΅ΡΡΡ Π»ΠΈΠ·ΠΎΡΠΎΠΌΠ°Π»ΡΠ½ΠΎΠΉ Π΄Π΅Π³ΡΠ°Π΄Π°ΡΠΈΠΈ, Π² ΡΠΎ Π²ΡΠ΅ΠΌΡ ΠΊΠ°ΠΊ ΠΎΡΡΠ°Π»ΡΠ½ΡΠ΅, ΡΠ°ΠΊ ΠΆΠ΅, ΠΊΠ°ΠΊ ΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡ Ρ Π½Π΅Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ Π’Π, ΡΠ΅ΡΠΈΠΊΠ»ΠΈΡΡΡΡ ΠΈΠ· ΡΠ°Π½Π½ΠΈΡ ΡΠ½Π΄ΠΎΡΠΎΠΌ ΠΎΠ±ΡΠ°ΡΠ½ΠΎ Π² ΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΡΡ ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Ρ. ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ Π² ΡΠ°Π½Π½ΠΈΡ ΡΠ½Π΄ΠΎΡΠΎΠΌΠ°Ρ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ Π΄ΠΎΡΡΠ°ΡΠΎΡΠ½ΠΎ Π΄ΠΎΠ»Π³ΠΎΠ΅ Π²ΡΠ΅ΠΌΡ ΡΠΊΡΠΏΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ Π² ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΡ Π‘-ΠΊΠΎΠ½ΡΠ΅Π²ΡΠΌ ΡΡΠ°ΡΡΠΊΠΎΠΌ, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠΌ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ Π’Π ΠΈ ΡΠΏΠΎΡΠΎΠ±Π΅Π½ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΎΠ²Π°ΡΡ Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠΌΠΈ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΠΌΠΈ ΡΡΠ±ΡΡΡΠ°ΡΠ°ΠΌΠΈ (Kay et al., 1986; ΠΠΎΡΠ½ΠΈΠ»ΠΎΠ²Π° ΠΈ Π΄Ρ., 1987). ΠΡΠ΅Π²ΠΈΠ΄Π½ΠΎ, ΡΡΠΎ ΡΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΠ΅ ΠΌΠ΅ΠΆΠ΄Ρ ΡΠ΅ΡΠΈΠΊΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ ΠΈ Π΄Π΅Π³ΡΠ°Π΄Π°ΡΠΈΠ΅ΠΉ ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ΅Ρ Π² Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΠΌΠ΅ΡΠ΅ Π΄Π»ΠΈΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΈ/ΠΈΠ»ΠΈ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΡ Π³Π΅Π½Π΅ΡΠΈΡΡΠ΅ΠΌΠΎΠ³ΠΎ Π½Π° ΠΠ ΠΈΠ»ΠΈ Π² ΡΠ°Π½Π½ΠΈΡ ΡΠ½Π΄ΠΎΡΠΎΠΌΠ°Ρ ΡΠΈΠ³Π½Π°Π»Π°. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, ΡΡΠ΅Π·Π²ΡΡΠ°ΠΉΠ½ΠΎ Π²Π°ΠΆΠ½ΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ ΠΏΡΠΈΠΎΠ±ΡΠ΅ΡΠ°ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΠ°ΠΊΠΈΡ ΡΡΠ°Π΄ΠΈΠΉ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π°, ΠΊΠ°ΠΊ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΡ ΠΈ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½Π°Ρ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠ° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ².
ΠΠ»Ρ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΉ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΈ Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΠΎ Π½Π°Π»ΠΈΡΠΈΠ΅ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠΉ Π’Π ΠΈ Π‘-ΠΊΠΎΠ½ΡΠ΅Π²ΠΎΠ³ΠΎ Π΄ΠΎΠΌΠ΅Π½Π° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° (Π‘ΠΎΠΊΠΎΠ»ΠΎΠ²Π° ΠΈ Π΄Ρ., 1995; Kornilova et al., 1996). ΠΠΎΠΆΠ½ΠΎ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°ΡΡ, ΡΡΠΎ Π’Π Π² Π΄Π°Π½Π½ΠΎΠΌ ΡΠ»ΡΡΠ°Π΅ Π½ΡΠΆΠ½Π° Π΄Π»Ρ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ ΠΏΠΎΡΡΠ΅Π΄ΡΡΠ²ΠΎΠΌ ΠΠ€Π -Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π½Π΅ΠΊΠΎΠ΅Π³ΠΎ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π½ΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ° (ΠΈΠ»ΠΈ Π±Π΅Π»ΠΊΠΎΠ²), ΠΎΠΏΠΎΡΡΠ΅Π΄ΡΡΡΠ΅Π³ΠΎ ΠΏΠ΅ΡΠ΅Ρ ΠΎΠ΄ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΈΠ· ΡΠ°Π½Π½ΠΈΡ Π² ΠΏΠΎΠ·Π΄Π½ΠΈΠ΅ ΡΠ½Π΄ΠΎΡΠΎΠΌΡ. Π ΡΡΠΎΠΌ ΡΠΌΡΡΠ»Π΅ ΠΌΠΎΠΆΠ½ΠΎ Π³ΠΎΠ²ΠΎΡΠΈΡΡ ΠΎ ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ, Π’Π-Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΈ.
Π ΡΡΠ΄Π΅ ΡΠ°Π±ΠΎΡ Π±ΡΠ»ΠΎ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π’Π-Π·Π°Π²ΠΈΡΠΈΠΌΠ°Ρ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠ° ΡΠ²Π»ΡΠ΅ΡΡΡ Π½Π°ΡΡΡΠ°Π΅ΠΌΠΎΠΉ ΠΏΡΠΈ ΠΎΡΠ½ΠΎΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π½ΠΈΠ·ΠΊΠΈΡ (1−10 Π½Π) ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·ΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ ΠΠ€Π , ΠΏΡΠΈ ΠΊΠΎΡΠΎΡΡΡ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΠ΅ Ρ ΠΏΠΎΠ²Π΅ΡΡ Π½ΠΎΡΡΠ½ΡΠΌΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°ΠΌΠΈ Π΅ΡΠ΅ Π΄Π°Π»Π΅ΠΊΠΎ ΠΎΡ Π½Π°ΡΡΡΠ΅Π½ΠΈΡ (ΠΠ΄ΠΎΠ²ΠΈΠ½Π° ΠΈ Π΄Ρ., 1993; French et al., 1994). ΠΠ΄Π½Π°ΠΊΠΎ ΠΈ ΠΏΡΠΈ Π²ΡΡΠΎΠΊΠΈΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ ΠΠ€Π , Ρ. Π΅. ΠΏΡΠΈ Π²ΡΡΠΎΠΊΠΎΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ Π·Π°Π½ΡΡΠΎΡΡΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ², ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΡ ΠΈ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠ°, Π½ΠΎ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΡ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π° Π² Π΄Π°Π½Π½ΠΎΠΌ ΡΠ»ΡΡΠ°Π΅ ΠΎΡΠ»ΠΈΡΠ°ΡΡΡΡ ΠΎΡ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠΎΠ² Π’Π-Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠ³ΠΎ ΠΏΡΡΠΈ. ΠΡΠΎΡ, ΡΠ°ΠΊ Π½Π°Π·ΡΠ²Π°Π΅ΠΌΡΠΉ Π’Π-Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΠΉ ΠΏΡΡΡ, ΠΏΠΎ ΡΡΠ΄Ρ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊ ΡΡ ΠΎΠΆ Ρ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠΌ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π° ΠΆΠΈΠ΄ΠΊΠΎΡΠ°Π·Π½ΡΡ ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΠΈ Π»ΠΈΠ³Π°Π½Π΄ΠΎΠ² ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ², Π½Π΅ ΠΈΠΌΠ΅ΡΡΠΈΡ Π’Π Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ (ΡΠ°ΠΊΠΈΡ , ΠΊΠ°ΠΊ Π»ΠΈΠΏΠΎΠΏΡΠΎΡΠ΅ΠΈΠ½Ρ Π½ΠΈΠ·ΠΊΠΎΠΉ ΠΏΠ»ΠΎΡΠ½ΠΎΡΡΠΈ (ΠΠΠ), Π°ΡΠΈΠ°Π»ΠΎΠ³Π»ΠΈΠΊΠΎΠΏΡΠΎΡΠ΅ΠΈΠ½Ρ), ΠΎΠ΄Π½Π°ΠΊΠΎ ΠΎΠ½ ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ Ρ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ Π½Π° ΠΏΠΎΡΡΠ΄ΠΎΠΊ Π½ΠΈΠΆΠ΅ (ΠΠ΄ΠΎΠ²ΠΈΠ½Π° ΠΈ Π΄Ρ., 1993). ΠΠΎΠ½ΠΊΡΠ΅ΡΠ½ΡΠ΅ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΡ ΠΎΠ±ΠΎΠΈΡ ΡΠΈΠΏΠΎΠ² ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΈ ΠΊ Π½Π°ΡΡΠΎΡΡΠ΅ΠΌΡ ΠΌΠΎΠΌΠ΅Π½ΡΡ Π½Π΅ΠΈΠ·Π²Π΅ΡΡΠ½Ρ, Π½ΠΎ ΠΌΠΎΠΆΠ½ΠΎ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»Π°Π³Π°ΡΡ, ΡΡΠΎ Π² ΠΏΠΎΡΠ»Π΅Π΄Π½Π΅ΠΌ ΡΠ»ΡΡΠ°Π΅ ΠΏΠ΅ΡΠ΅Ρ ΠΎΠ΄ Π² ΠΏΠΎΠ·Π΄Π½ΠΈΠ΅ ΡΠ½Π΄ΠΎΡΠΎΠΌΡ ΠΎΡΡΡΠ΅ΡΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠΎΠ»ΡΠΊΠΎ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΡΠ½ΠΈΠ²Π΅ΡΡΠ°Π»ΡΠ½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ Π±Π΅Π»ΠΊΠΎΠ²-ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠΎΠ² Π²Π΅Π·ΠΈΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ°, Π±Π΅Π· Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½ΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠΎΡΡΠΈΡΡΡΡΠΈΡ Π±Π΅Π»ΠΊΠΎΠ². ΠΠ·Π°ΠΈΠΌΠΎΠΎΡΠ½ΠΎΡΠ΅Π½ΠΈΡ ΠΌΠ΅ΠΆΠ΄Ρ Π΄Π²ΡΠΌΡ ΡΠΈΡΡΠ΅ΠΌΠ°ΠΌΠΈ Π°Π±ΡΠΎΠ»ΡΡΠ½ΠΎ Π½Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Ρ, Π½Π΅ ΠΈΠ·Π²Π΅ΡΡΠ½Ρ ΡΠ°ΠΊΠΆΠ΅ ΠΈ Π±Π΅Π»ΠΊΠΈ-ΠΌΠΈΡΠ΅Π½ΠΈ Π’Π ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ°, Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½Π½ΡΠ΅ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΈ.
ΠΠ°Π²ΠΈΡΠΈΠΌΠΎΡΡΡ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΈ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΎΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π΅Π³ΠΎ Π’Π ΡΠΊΠ°Π·ΡΠ²Π°Π΅Ρ Π½Π° ΡΠΎ, ΡΡΠΎ Π±Π΅Π»ΠΊΠΈ-ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΡ ΡΡΠΈΡ ΡΡΠ°Π΄ΠΈΠΉ ΡΠ²Π»ΡΡΡΡΡ Π΅Π΅ ΡΡΠ±ΡΡΡΠ°ΡΠ°ΠΌΠΈ. Π‘Π΅ΠΉΡΠ°Ρ ΠΈΠ·Π²Π΅ΡΡΠ΅Π½ ΡΠ΅Π»ΡΠΉ ΡΡΠ΄ ΡΠ°ΠΊΠΈΡ ΡΡΠ±ΡΡΡΠ°ΡΠΎΠ². ΠΡΠΎ Π°Π΄Π°ΠΏΡΠΎΡΠ½ΡΠ΅ Π±Π΅Π»ΠΊΠΈ She, GRB2, ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΠΎΠ½Π½ΡΠ΅ ΡΠ°ΠΊΡΠΎΡΡ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° STAT, ΡΠΎΡΡΠΎΠ»ΠΈΠΏΠ°Π·Π° Π‘Ρ (Π€ΠΠ‘Ρ), ΡΠΎΡΡΠ°ΡΠΈΠ΄ΠΈΠ»ΠΈΠ½ΠΎΠ·ΠΈΡΠΎΠ»-3-ΠΊΠΈΠ½Π°Π·Π° (Π€Π-Π-Π) ΠΈ Src-ΠΊΠΈΠ½Π°Π·Π°, Π° ΡΠ°ΠΊΠΆΠ΅ ΡΡΠ΄ Π΄ΡΡΠ³ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² (Moghal, Sternberg, 1999). ΠΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ Π²Π΅ΡΡΠΌΠ° ΠΈΠ½ΡΠ΅ΡΠ΅ΡΠ½ΡΠΌ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΡΠ°ΡΡΠΈΡ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π° ΠΈΠ·Π²Π΅ΡΡΠ½ΡΡ ΡΠΈΠ³Π½Π°Π»ΡΠ½ΡΡ Π±Π΅Π»ΠΊΠΎΠ², Π°ΠΊΡΠΈΠ²ΠΈΡΡΠ΅ΠΌΡΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠΌ ΠΠ€Π , ΡΠ΅ΠΌ Π±ΠΎΠ»Π΅Π΅ ΡΡΠΎ ΠΈΠΌΠ΅ΡΡΡΡ Π΄Π°Π½Π½ΡΠ΅ ΠΎ Π²ΠΎΠ²Π»Π΅ΡΠ΅Π½ΠΈΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ ΠΈΠ· Π½ΠΈΡ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ ΡΡΠ°Π½ΡΠΏΠΎΡΡΠ½ΡΡ ΠΏΡΡΠ΅ΠΉ. ΠΠ°ΠΏΡΠΈΠΌΠ΅Ρ, ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π΄ΡΠΎΠΆΠΆΠ΅Π²ΠΎΠΉ Π±Π΅Π»ΠΎΠΊ VPS34, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΠΉ Π€Π-Π-ΠΊΠΈΠ½Π°Π·Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ, ΡΠ΅Π³ΡΠ»ΠΈΡΡΠ΅Ρ ΡΡΠ°Π½ΡΠΏΠΎΡΡ ΠΌΠ΅ΠΆΠ΄Ρ ΠΏΠΎΠ·Π΄Π½ΠΈΠΌΠΈ ΡΠ½Π΄ΠΎΡΠΎΠΌΠ°ΠΌΠΈ ΠΈ Π²Π°ΠΊΡΠΎΠ»ΡΡ (Schu et al., 1993). Π‘ΡΡΠ΅ΡΡΠ²ΡΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ, ΠΏΠΎΡΠ²ΡΡΠ΅Π½Π½ΡΠ΅ ΡΠΎΠ»ΠΈ Π€Π-Π-Π Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² ΡΠΎΡΡΠΎΠ²ΡΡ ΡΠ°ΠΊΡΠΎΡΠΎΠ², ΠΎΠ΄Π½Π°ΠΊΠΎ ΠΎΠ½ΠΈ ΠΌΠ°Π»ΠΎΡΠΈΡΠ»Π΅Π½Π½Ρ ΠΈ ΠΈΡΡΠ΅ΡΠΏΡΠ²Π°ΡΡΡΡ Π΄Π²ΡΠΌΡ ΡΠ°Π±ΠΎΡΠ°ΠΌΠΈ ΠΎ Π²Π»ΠΈΡΠ½ΠΈΠΈ Π²ΠΎΡΡΠΌΠ°Π½Π½ΠΈΠ½Π° (ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° Π€Π-Π-Π) Π½Π° ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ· ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠΎΠ² ΡΠ°ΠΊΡΠΎΡΠ° ΡΠΎΡΡΠ°, Π²ΡΠ΄Π΅Π»ΡΠ΅ΠΌΠΎΠ³ΠΎ ΡΡΠΎΠΌΠ±ΠΎΡΠΈΡΠ°ΠΌΠΈ (Π€Π ΠΠ’) (Joly et al., 1995; Shpetner et al., 1996). ΠΠ΄Π½Π°ΠΊΠΎ Π² Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΠ΅ Π½Π΅Ρ Π΄Π°Π½Π½ΡΡ ΠΎ ΡΠΎΠ»ΠΈ Π€Π-Π-Π Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π° ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΠ€Π .
Π ΠΏΠΎΡΠ»Π΅Π΄Π½ΠΈΠ΅ Π³ΠΎΠ΄Ρ ΠΏΠΎΡΠ²ΠΈΠ»ΠΈΡΡ ΡΠ°ΠΊΠΆΠ΅ ΡΠ°Π±ΠΎΡΡ, Π² ΠΊΠΎΡΠΎΡΡΡ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Src-ΠΊΠΈΠ½Π°Π·Π°, Π°ΠΊΡΠΈΠ²ΠΈΡΡΡΡΠ°ΡΡΡ ΠΠ€Π -Π·Π°Π²ΠΈΡΠΈΠΌΡΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, ΠΌΠΎΠΆΠ΅Ρ ΡΡΠ°ΡΡΠ²ΠΎΠ²Π°ΡΡ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° (Ware et al., 1997). Π‘ΡΡΠ΅ΡΡΠ²ΡΡΡ Π΄Π°Π½Π½ΡΠ΅ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½Π°Ρ Src-ΠΊΠΈΠ½Π°Π·Π° ΡΠΏΠΎΡΠΎΠ±Π½Π° ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°ΡΡ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΊΠ»Π°ΡΡΠΈΠ½ (Π±Π΅Π»ΠΎΠΊ, ΠΊΠΎΡΠΎΡΡΠΉ Π²Ρ ΠΎΠ΄ΠΈΡ Π² ΡΠΎΡΡΠ°Π² ΠΎΠΊΠ°ΠΉΠΌΠ»Π΅Π½ΠΈΡ ΡΠΌΠΎΠΊ ΠΈ Π²Π΅Π·ΠΈΠΊΡΠ», ΡΠ΅ΡΠ΅Π· ΠΊΠΎΡΠΎΡΡΠ΅ Π² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΌ ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ ΠΏΠΎΡΡΡΠΏΠ»Π΅Π½ΠΈΠ΅ ΡΡΠ΄Π° Π²ΡΡΠΎΠΊΠΎΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΡ Π²Π΅ΡΠ΅ΡΡΠ² Π² ΠΊΠ»Π΅ΡΠΊΡ) ΠΈ Π²ΡΠ·ΡΠ²Π°ΡΡ Π΅Π³ΠΎ ΠΏΠ΅ΡΠ΅ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΊ ΠΠ (Wilde et al., 1999), ΡΠ΅ΠΌ ΡΠ°ΠΌΡΠΌ ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Ρ ΡΠΈΡΠ»ΠΎ ΠΠ― ΠΈ ΡΡΠΊΠΎΡΡΡ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΡ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΠ€Π . Π ΡΠΎΠΌΡ ΠΆΠ΅, Π±ΡΠ»ΠΎ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½Π°Ρ Src-ΠΊΠΈΠ½Π°Π·Π° ΡΠΏΠΎΡΠΎΠ±Π½Π° ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°ΡΡ Π΄ΠΈΠ½Π°ΠΌΠΈΠ½ — Π±Π΅Π»ΠΎΠΊ, ΠΈΠ³ΡΠ°ΡΡΠΈΠΉ ΠΊΠ»ΡΡΠ΅Π²ΡΡ ΡΠΎΠ»Ρ Π² ΠΏΡΠΎΡΠ΅ΡΡΠ΅ Π·Π°ΠΌΡΠΊΠ°Π½ΠΈΡ ΠΠ― ΠΈ ΠΏΡΠ΅Π²ΡΠ°ΡΠ΅Π½ΠΈΡ Π΅Π΅ Π² ΠΎΠΊΠ°ΠΉΠΌΠ»Π΅Π½Π½ΡΡ Π²Π΅Π·ΠΈΠΊΡΠ»Ρ (Ahn et al., 1999). ΠΠ΄Π½Π°ΠΊΠΎ, Π²ΠΎ-ΠΏΠ΅ΡΠ²ΡΡ , ΡΠΏΠΎΠΌΡΠ½ΡΡΡΠ΅ ΡΠ°Π±ΠΎΡΡ ΡΠΎΠ΄Π΅ΡΠΆΠ°Ρ ΡΠ΅Π»ΡΠΉ ΡΡΠ΄ Π²Π½ΡΡΡΠ΅Π½Π½ΠΈΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΡΠ΅ΡΠΈΠΉ, Π²ΠΎ-Π²ΡΠΎΡΡΡ , ΡΠΎΠ²Π΅ΡΡΠ΅Π½Π½ΠΎ Π½Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ Π²ΠΎΠΏΡΠΎΡ ΠΎ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠΌ Π²Π»ΠΈΡΠ½ΠΈΠΈ Src Π½Π° Π΄ΡΡΠ³ΠΈΠ΅ ΡΡΠ°Π΄ΠΈΠΈ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π°.
Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, Π²ΠΎΠΏΡΠΎΡ ΠΎ ΡΠΎΠ»ΠΈ Π€Π-Π-ΠΊΠΈΠ½Π°Π·Ρ ΠΈ Src-ΠΊΠΈΠ½Π°Π·Ρ Π² ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·Π΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΠ€Π ΠΎΡΡΠ°Π΅ΡΡΡ Π½Π΅ΡΠ΅ΡΠ΅Π½Π½ΡΠΌ.
Π²ΡΠ²ΠΎΠ΄Ρ.
1. ΠΡΡΡΡΡΡΠ²ΠΈΠ΅ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ c-Src ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ Π½Π΅ Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΡΠΊΠΎΡΠΎΡΡΡ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΈ ΡΠ΅ΡΠΈΠΊΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ², ΠΈ Π»ΠΈΡΡ Π² Π½Π΅Π·Π½Π°ΡΠΈΡΠ΅Π»ΡΠ½ΠΎΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ ΠΏΠΎΠ΄Π°Π²Π»ΡΠ΅Ρ ΠΈΡ Π΄Π΅Π³ΡΠ°Π΄Π°ΡΠΈΡ.
2. ΠΠ΅ΠΉΡΡΠ²ΠΈΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Src-ΠΊΠΈΠ½Π°Π·Ρ CGP77675 ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ Π΄ΠΎΡΡΠΎΠ²Π΅ΡΠ½ΠΎΠΌΡ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ ΡΠΊΠΎΡΠΎΡΡΠΈ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ, ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ ΡΠΊΠΎΡΠΎΡΡΠΈ ΡΠ΅ΡΠΈΠΊΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΠΏΠ°Π΄Π΅Π½ΠΈΡ ΡΠΊΠΎΡΠΎΡΡΠ΅ΠΉ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΈ ΠΈ Π΄Π΅Π³ΡΠ°Π΄Π°ΡΠΈΠΈ, Π½ΠΎ ΡΡΡΠ΅ΠΊΡ Π½Π΅ ΠΏΡΠ΅Π²ΡΡΠ°Π΅Ρ Π² ΡΡΠ΅Π΄Π½Π΅ΠΌ 20−30% ΠΎΡ ΠΊΠΎΠ½ΡΡΠΎΠ»Ρ. ΠΠΎΠ»Π΅Π΅ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ CGP77675 ΠΌΠΎΠΆΠ΅Ρ ΠΎΠ±ΡΡΡΠ½ΡΡΡΡΡ ΡΠ΅ΠΌ, ΡΡΠΎ ΡΡΠΎΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡ Π²Π»ΠΈΡΠ΅Ρ Π½Π° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ ΡΠ°ΠΌΠΎΠ³ΠΎ c-Src, Π½ΠΎ ΡΠ°ΠΊΠΆΠ΅ ΠΈ Π΄ΡΡΠ³ΠΈΡ ΡΠ»Π΅Π½ΠΎΠ² ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π° Src-ΠΏΠΎΠ΄ΠΎΠ±Π½ΡΡ ΠΊΠΈΠ½Π°Π·, Π² ΡΠ°ΡΡΠ½ΠΎΡΡΠΈ, Lck ΠΈ Yes. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, ΠΎΡΡΡΡΡΡΠ²ΠΈΠ΅ Src-ΠΊΠΈΠ½Π°Π·Ρ ΠΌΠΎΠΆΠ΅Ρ ΠΊΠΎΠΌΠΏΠ΅Π½ΡΠΈΡΠΎΠ²Π°ΡΡΡΡ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Π΄ΡΡΠ³ΠΈΡ ΠΊΠΈΠ½Π°Π· ΡΡΠΎΠ³ΠΎ ΡΠ΅ΠΌΠ΅ΠΉΡΡΠ²Π°.
3. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΡΠΈΠΌΡΠ»ΡΡΠΈΡ ΠΈΠ½ΡΠ΅ΡΠ½Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² Π½Π΅ ΡΠ²ΡΠ·Π°Π½Π° Ρ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ΠΌ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΠΈ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΠ― ΠΈ Π½Π΅ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ Π°ΡΡΠΎΡΠΈΠ°ΡΠΈΠΈ ΠΊΠ»Π°ΡΡΠΈΠ½Π° Ρ ΠΠ. ΠΡΠΎΡ ΡΠ°ΠΊΡ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΠ΅Ρ ΠΎ ΡΠΎΠΌ, ΡΡΠΎ Π°ΠΊΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½Π½ΡΠ΅ ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΡ ΠΠ€Π Π½Π΅ ΡΠ²Π»ΡΡΡΡΡ ΡΠ°ΠΉΡΠ°ΠΌΠΈ ΠΈΠ½ΠΈΡΠΈΠ°ΡΠΈΠΈ ΡΠ±ΠΎΡΠΊΠΈ ΠΠ―.
4. ΠΠΎΡΡΠΌΠ°Π½Π½ΠΈΠ½, ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡ Π€Π-Π-Π, ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ ΠΏΠΎΠ»Π½ΠΎΡΡΡΡ Π±Π»ΠΎΠΊΠΈΡΡΠ΅Ρ ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΡ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ², Ρ. Π΅. ΠΏΠ΅ΡΠ΅Ρ ΠΎΠ΄ ΠΈΠ· ΡΠ°Π½Π½ΠΈΡ Π² ΠΏΠΎΠ·Π΄Π½ΠΈΠ΅ ΡΠ½Π΄ΠΎΡΠΎΠΌΡ, Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ ΡΠΏΠΈΠ΄Π΅ΡΠΌΠΎΠΈΠ΄Π½ΠΎΠΉ ΠΊΠ°ΡΡΠΈΠ½ΠΎΠΌΡ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° Π»ΠΈΠ½ΠΈΠΈΠ431.
5. ΠΡΡΠ΅ΠΊΡ ΡΠΎΠΊΡΠΈΠ½Π° ΠΏΡΠΎΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΠΏΡΠΈ Π½ΠΈΠ·ΠΊΠΈΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ ΠΠ€Π , ΠΊΠΎΠ³Π΄Π° ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΡΠ΅Ρ Π² ΠΎΡΠ½ΠΎΠ²Π½ΠΎΠΌ ΠΠ€Π -ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠ°Ρ, Π’Π-Π·Π°Π²ΠΈΡΠΈΠΌΠ°Ρ ΡΠΈΡΡΠ΅ΠΌΠ° ΡΠΎΡΡΠΈΡΠΎΠ²ΠΊΠΈ. Π‘ΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π²ΠΎΡΡΠΌΠ°Π½Π½ΠΈΠ½Π° Π½Π° ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ· ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ° ΠΠ€Π ΠΏΡΠΈ Π½ΠΈΠ·ΠΊΠΈΡ ΠΈ Π²ΡΡΠΎΠΊΠΈΡ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΡΡ Π»ΠΈΠ³Π°Π½Π΄Π° ΠΏΠΎΠ·Π²ΠΎΠ»ΡΡΡ Π³ΠΎΠ²ΠΎΡΠΈΡΡ ΠΎ Π€Π-Π-ΠΊΠΈΠ½Π°Π·Π΅ ΠΊΠ°ΠΊ ΠΎ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΠ»Π΅ΠΌΠ΅Π½ΡΠ΅ Π’Π-Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠΉ ΡΠΎΡΡΠΈΡΡΡΡΠ΅ΠΉ ΡΠΈΡΡΠ΅ΠΌΡ.
6. ΠΠΎΡΡΠΌΠ°Π½Π½ΠΈΠ½ Π²ΡΠ·ΡΠ²Π°Π΅Ρ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΌΠΎΡΡΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡ-ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ ΡΠ°Π½Π½ΠΈΡ ΡΠ½Π΄ΠΎΡΠΎΠΌ, Π° ΠΈΠΌΠ΅Π½Π½ΠΎ, ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ ΠΈΡ ΡΠ°Π·ΠΌΠ΅ΡΠ° ΠΈ ΡΠΌΠ΅Π½ΡΡΠ΅Π½ΠΈΠ΅ ΡΠΈΡΠ»Π°. ΠΡΠΈ ΡΡΠΎΠΌ, ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ Π½Π°ΠΊΠΎΠΏΠ»Π΅Π½ΠΈΠ΅ ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² Π² ΠΎΠΊΠΎΠ»ΠΎΡΠ΄Π΅ΡΠ½ΠΎΠΉ ΠΎΠ±Π»Π°ΡΡΠΈ, ΠΊΠΎΡΠΎΡΡΡ ΡΠ°ΡΡΠΌΠ°ΡΡΠΈΠ²Π°ΡΡ ΠΊΠ°ΠΊ ΠΎΠ±Π»Π°ΡΡΡ ΠΏΠΎΠ·Π΄Π½ΠΈΡ ΡΠ½Π΄ΠΎΡΠΎΠΌ. ΠΠ΄Π½Π°ΠΊΠΎ, ΠΏΠΎ Π΄Π°Π½Π½ΡΠΌ ΡΡΠ±ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΡΠ°ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΎΡΠ³Π°Π½Π΅Π»Π» Π² Π³ΡΠ°Π΄ΠΈΠ΅Π½ΡΠ΅ ΠΠ΅ΡΠΊΠΎΠ»Π»Π°, ΠΠ€Π -ΡΠ΅ΡΠ΅ΠΏΡΠΎΡΠ½ΡΠ΅ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΡ Π»ΠΎΠΊΠ°Π»ΠΈΠ·ΡΡΡΡΡ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ Π² ΡΠ°Π½Π½ΠΈΡ ΡΠ½Π΄ΠΎΡΠΎΠΌΠ°Ρ ΠΈ ΠΏΠ΅ΡΠ΅Ρ ΠΎΠ΄Π° Π² ΠΏΠΎΠ·Π΄Π½ΠΈΠ΅ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ Π½Π΅ ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ. Π’Π°ΠΊΠΈΠΌ ΠΎΠ±ΡΠ°Π·ΠΎΠΌ, ΡΠ°Π½Π½ΠΈΠ΅ ΡΠ½Π΄ΠΎΡΠΎΠΌΡ ΠΌΠΎΠ³ΡΡ ΠΈΠΌΠ΅ΡΡ ΠΎΠΊΠΎΠ»ΠΎΡΠ΄Π΅ΡΠ½ΡΡ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΡ.
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